Recently, Professor Xu Chuan's team from Jinfeng Laboratory Yuyu and Guangdong Pathology Research Center published the latest research results on Oncogene, clarifying the clinical drug Cephalanthine, CEP) can significantly improve the therapeutic response of microsatellite-stable colorectal cancer (MSS-CRC) to PD-1 inhibitors by inducing immunogenic cell death (ICD).

Colorectal cancer (CRC) has become a major public health issue that threatens human health. In recent years, anti-PD-1/PD-L1 therapy has made breakthrough progress in CRC treatment, but has only been approved for use in highly unstable microsatellite patients with 15% of microsatellites, while microsatellite-stable patients (MSS-CRC) that account for the majority of CRC have no significant response. Traditional theory believes that lack of neoantigens in tumors is an important reason for the resistance to MSS-CRC immunotherapy. Latest research shows that MSS-CRC low expression of tumor neoantigens and insufficient presentation efficiency is an important reason for immunotherapy resistance. Therefore, enhancing the presentation efficiency of low-expressed tumor neoantigens is a potential breakthrough in solving the dilemma of MSS-CRC immunotherapy.

▲Schematic diagram of the efficacy of PD-1 inhibitors inducing immunogenic cell death by inhibiting autophagy flow.

Through high-throughput drug screening, the team found that the clinically approved whitening drug Qianjinxin (CEP) can significantly promote the expression of calreticin (CRT) on the surface of tumor cells, thus exposing the "eat me" signal, accompanied by the release of ATP and HMGB1, thereby inducing DC maturation and antigen presentation. Animal experiments further confirmed that CEP-treated CT26 cells can be used as vaccines to effectively inhibit tumor formation. Mechanism studies have shown that CEP blocks autophagy flow by inhibiting autophagosome-lysosome fusion, triggers endoplasmic reticulum stress, and ultimately induces ICD. It is worth noting that while CEP activates anti-tumor immunity, it compensatory upregulates PD-L1 expression. This discovery explains the limited efficacy of CEP single agent, and also provides a theoretical basis for combined treatment: CEP increases the proportion of activated DCs in tumors and activates T cell immune responses, while PD-1 inhibitors relieve T cell function inhibition and increase IFNγ+ CD8+ The proportion of T cells significantly inhibits tumor growth.

Qianjin Tengsu is a clinically approved whitening drug used to treat leukopenia caused by oncology radiotherapy and chemotherapy, with clear clinical safety. This study provides a new theoretical basis for it as an anti-tumor adjuvant drug and shows broad clinical application prospects.

Oncogene by Springer Nature Publishing Group publishes, focusing on the fields of cancer biology and tumor translational medicine, covering multiple disciplines such as oncogenes, signal transduction, epigenetic regulation, tumor microenvironment, drug tolerance, etc., and the content takes into account basic molecular mechanism research and clinical transformation applications (such as targeted therapy, immunotherapy, and early diagnostic markers). The latest impact factor of the journal is 7.3, and it is Q1 in the JCR area. The latest upgraded version of major medicine in the Chinese Academy of Sciences is located in District 1, and is the core platform for global cancer researchers to publish breakthrough results.

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https://www.nature.com/articles/s41388-025-03488-9